It is known that living organisms react defensively against implanted artificial organs or medical devices to show prominent rejections such as blood coagulation, inflammation and encapsulation. This is a result of a series of bioactivation reactions that start from adsorption of proteins on materials constituting the artificial organs and medical devices. Accordingly, treatments with artificial organs or medical devices entail simultaneous use of drugs, for example anticoagulants such as heparin and immunosuppressants.
However, side effects of these drugs are more serious when the treatment extends over a long period of time or as patients advance in age.
To solve these problems, a series of medical materials known as biocompatible materials have been developed. Of such biocompatible materials, polymers having phosphorylcholine groups that are phospholipid polar groups have been developed focusing on the structure of biomembrane surfaces. In detail, polymers that have structural units from 2-methacryloyloxyethyl phosphorylcholine (MPC) (hereinafter “MPC polymers”) show particularly high biocompatibility (Non-Patent Document 1).
MPC is a methacrylate and homopolymers thereof are water soluble, whilst copolymers thereof with vinyl monomers are water-insoluble MPC polymers having a structure suitable for covering the surface of medical devices. By coating the device surface with the water-insoluble MPC polymers, blood coagulation can be prevented without anticoagulants, and subcutaneous implantation tests have proven very high biocompatibility (Non-Patent Document 2). The water-insoluble MPC polymers have been used as surface-coating materials for medical devices that are clinically applied in the United States and Europe. An increasing number of such coated devices have been approved also in Japan. The polymers are thus expected to dramatically improve the effectiveness of medical devices and to improve patient's quality of life.
However, mechanical strength, water resistance and autoclave sterilization heat resistance are still insufficient because of the MPC's inherent hydrophilicity and the flexible main chain structures of the MPC/vinyl copolymers. There is therefore a need for materials that exhibit improved mechanical strength, water resistance and heat resistance while maintaining the superior biocompatibility and processability of the MPC polymers.
The present inventors have reported specific diamine compounds having a phosphorylcholine group, and polymers from the compound as a monomer that have excellent water resistance, heat resistance and biocompatibility (Patent Document 1).
Non-Patent Document 1: Ishihara et al., Polymer Journal, Vol. 22, p. 355, 1990
Non-Patent Document 2: Ishihara et al., Geka (Surgery), Vol. 61, p. 132, 1999
Patent Document 1: WO 2004/074298
The diamine compounds, however, show relatively low reactivity in polymerization. Accordingly, there should be developed novel diamine compounds with a phosphorylcholine group that have higher polymerization reactivity (hereinafter, the highly polymerizable phosphorylcholine group-containing diamine compounds). With such highly polymerizable phosphorylcholine group-containing diamine compounds, it is expected that high-molecular weight polymers may be easily obtained and mechanical strength, water resistance, heat resistance and biocompatibility of the polymers may be improved, thereby increasing utility as materials.
It is therefore an object of the invention to provide highly polymerizable phosphorylcholine group-containing diamine compounds, high-molecular weight polymers from the highly polymerizable phosphorylcholine group-containing diamine compound as a monomer that achieve improved mechanical strength, water resistance and heat resistance while maintaining the excellent biocompatibility and processability of the MPC polymers, and processes for producing the polymers.
The present inventors diligently studied to achieve the above object in view of the aforesaid circumstances. They have then found that diamine compounds having a specific structure can give polymers capable of improved mechanical strength, water resistance, heat resistance and biocompatibility. The present invention has been completed based on the finding.